Alcaftadine is chemically 6,11 -dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde and is known from U.S. Pat. No. 5,468,743 and is represented by a compound of structural formula I:

Alcaftadine is a H1 histamine receptor antagonist sold in USA under the proprietary name of “LASTACAFT” and is indicated for the prevention of itching associated with allergic conjunctivitis.
The process of preparing alcaftadine compound of structural formula I is disclosed in U.S. Pat. No. 5,468,743 for preparing “alcaftadine analogous compound,” which is represented below in Scheme no. I, Scheme no. II and Scheme no. III. The alcaftadine obtained according to Scheme no. I, Scheme no. II and Scheme no. III is characterized by melting point of 171.6° C. (referred herein after as Form I).



A survey of the literature on alcaftadine did not provide any reference to its crystal structure or the possibility of different polymorphs. Information about the solid-state properties of a drug substance is important. For example, different forms may have significantly different solubilities. Further, the handling and stability of a drug substance may depend critically on the solid state of the drug.
Polymorphism is defined as “the ability of a compound to crystallize in more than one distinct crystal species” and different crystal arrangements of the same chemical compound are termed as polymorphs. Polymorphs of the same compound arise due to difference in the internal arrangement of atoms. Different polymorphs have different free energies and therefore have different physical properties such as solubility, chemical stability, melting point, density, flow properties, bioavailability and so forth.
The inventors of the present application have found that alcaftadine can exhibit polymorphism (i.e., alcaftadine can exist in different polymorphic forms) and accordingly, novel polymorphic forms of alcaftadine are provided.